US4659858A - Preparation of 2,3-dihydro-1,3,2-benzodiazaphosphole-2-oxides - Google Patents

Preparation of 2,3-dihydro-1,3,2-benzodiazaphosphole-2-oxides Download PDF

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US4659858A
US4659858A US06/811,067 US81106785A US4659858A US 4659858 A US4659858 A US 4659858A US 81106785 A US81106785 A US 81106785A US 4659858 A US4659858 A US 4659858A
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dihydro
benzodiazaphosphole
reaction
phosphite
oxides
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US06/811,067
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Kurt H. Pilgram
Richard D. Skiles
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Shell USA Inc
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Shell Oil Co
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6564—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms
    • C07F9/6581—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms
    • C07F9/6584—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and nitrogen atoms with or without oxygen or sulfur atoms, as ring hetero atoms having one phosphorus atom as ring hetero atom
    • C07F9/65848—Cyclic amide derivatives of acids of phosphorus, in which two nitrogen atoms belong to the ring

Definitions

  • This invention relates to a process for the preparation of 2,3-dihydro-1,3,2-benzodiazaphosphole-2-oxides.
  • dihydro-1,3,2-benzodiazaphosphole-2-oxides may be prepared by refluxing an addition product of phenylphosphonic dichloride with ortho-diamines in bromobenzene (J. Org. Chem., 26, 3995 (1961)).
  • This method of preparation has certain drawbacks.
  • ortho-diamines are difficult to make and are relatively unstable.
  • the preparative technique utilizing bromobenzene is tedious and often results in poor yields of the desired dihydro-1,3,2-benzodiazaphosphole-2-oxide product.
  • Nitrenes are generally obtained by a loss of nitrogen from an azide or by the removal of oxygen from nitroso or nitro compounds. Cyclization of nitrenes derived from 2-nitrophenyl sulfides has led to the formation of phenothiazines.
  • the analogous reaction of a 2-nitro-diphenylamine derivative with excess trialkyl phosphite did not yield the phenazine. Instead, an alternative nitrogen to phosphorous ring closure was achieved leading to the formation of dihydro-1,3,2-benzodiazaphosphole-2-oxide in high yield. This method of preparing dihydro-1,3,2-benzodiazaphosphole-2-oxides is much more efficient than methods previously used.
  • This invention relates to a process for preparing 1-alkyl-2-alkoxy-3-aryl-2,3-dihydro-1,3,2-benzodiazaphosphole-2-oxides by treating 2-nitrodiphenylamines with trialkyl phosphites at elevated temperature.
  • 1-alkyl-2-alkoxy-3-aryl-2,3-dihydro-1,3,2-benzodiazaphosphole-2-oxides can be prepared in high yield by treating 2-nitrodiphenylamines with trialkyl phosphites.
  • the 1-alkyl-2-alkoxy-3-aryl-2,3-dihydro-1,3,2,-benzodiazaphosphole-2-oxides prepared in this invention are defined generally by the formula ##STR1## wherein R is an alkyl containing from one to five carbon atoms and X and Y each represent substituents such as unsubstituted or halogen-substituted alkyl, alkenyl or alkoxy, cyano, alkylsulfonyl, alkoxycarbonyl or halo groups which do not interfere with the reaction.
  • Compounds of Formula I can be prepared by treating a 2-nitrodiphenylamine ##STR2## with a trialkyl phosphite, (RO) 3 P.
  • the trialkyl phosphite is preferably trimethyl phosphite or triethyl phosphite.
  • the 2-nitrodiphenylamine may carry substituents X and Y which may be, for example, unsubstituted or substituted alkyl or alkoxy, as well as other groups not interfering with the reaction. Depending on the nature of the X and Y substituents, trimethyl phosphite may be preferred in one reaction while triethyl phosphite may be preferred in another reaction.
  • the time required for the reaction to occur as well as the yield of the desired 1-alkyl-2-alkoxy-3-aryl-2,3-dihydro-1,3,2-benzodiazaphosphole-2-oxide product are different for reactions utilizing trimethyl phosphite and reactions utilizing triethyl phosphite.
  • the structure of the products formed in the instant invention was determined by conventional analytical techniques, infrared spectroscopy, mass spectroscopy, and NMR spectroscopy.
  • the reaction of 2-nitrodiphenylamine with trimethyl phosphite proceeds according to the equation: ##STR3##
  • the reaction is carried out at elevated temperature, preferably about 80° C. to about 160° C.
  • the length of time required to complete the reaction is dependent upon the temperature.
  • the reaction proceeds with trimethyl phosphate and dimethyl methyl phosphonate being the only reaction products formed in addition to 1-alkyl-2-alkoxy-3-aryl-2,3-dihydro-1,3,2-benzodiazaphosphole-2-oxide.
  • continued heating at temperatures ranging from about 190° C.
  • reaction of 2-nitrodiphenylamine with triethyl phosphite leads to the formation of a phosporamidate and 2,3-dihydro-1,3,2-benzodiazaphosphole-2-oxide derivative.
  • the reaction proceeds according to the equation: ##STR4## The reaction is carried out at a temperature ranging from about 130° C. to about 165° C. The length of time required for the desired reaction to occur is dependent on temperature and is not critical. When the reaction temperature is maintained at reflux over prolonged periods of time (3-5 days), which is about 180° C.
  • the products formed are 2-(diethylamino)diphenylamine, 2-(diethylamino)-N-ethyldiphenylamine, and a mixture of tetraethylated ortho-aminodiphenylamines.
  • Compounds prepared by the process of the invention are suitable for use as intermediates for pharmaceuticals as well as organic ligands such as, for example, a phosphine ligand in a carbonylation reaction.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)

Abstract

A process for the preparation of 2,3-dihydro-1,3,2-benzodiazaphosphole-2-oxides which comprises reacting 2-nitrodiphenylamine with a trialkyl phosphite at elevated temperature.

Description

FIELD OF THE INVENTION
This invention relates to a process for the preparation of 2,3-dihydro-1,3,2-benzodiazaphosphole-2-oxides.
BACKGROUND OF THE INVENTION
It is known that dihydro-1,3,2-benzodiazaphosphole-2-oxides may be prepared by refluxing an addition product of phenylphosphonic dichloride with ortho-diamines in bromobenzene (J. Org. Chem., 26, 3995 (1961)). This method of preparation, however, has certain drawbacks. For example, ortho-diamines are difficult to make and are relatively unstable. Also, the preparative technique utilizing bromobenzene is tedious and often results in poor yields of the desired dihydro-1,3,2-benzodiazaphosphole-2-oxide product.
It was thought that a synthesis involving intramolecular cyclization of nitrenes derived from 2-nitrodiphenylamine derivatives would yield phenazines. Nitrenes are generally obtained by a loss of nitrogen from an azide or by the removal of oxygen from nitroso or nitro compounds. Cyclization of nitrenes derived from 2-nitrophenyl sulfides has led to the formation of phenothiazines. The analogous reaction of a 2-nitro-diphenylamine derivative with excess trialkyl phosphite did not yield the phenazine. Instead, an alternative nitrogen to phosphorous ring closure was achieved leading to the formation of dihydro-1,3,2-benzodiazaphosphole-2-oxide in high yield. This method of preparing dihydro-1,3,2-benzodiazaphosphole-2-oxides is much more efficient than methods previously used.
SUMMARY OF THE INVENTION
This invention relates to a process for preparing 1-alkyl-2-alkoxy-3-aryl-2,3-dihydro-1,3,2-benzodiazaphosphole-2-oxides by treating 2-nitrodiphenylamines with trialkyl phosphites at elevated temperature.
DESCRIPTION OF THE INVENTION
It has been found that 1-alkyl-2-alkoxy-3-aryl-2,3-dihydro-1,3,2-benzodiazaphosphole-2-oxides can be prepared in high yield by treating 2-nitrodiphenylamines with trialkyl phosphites.
The 1-alkyl-2-alkoxy-3-aryl-2,3-dihydro-1,3,2,-benzodiazaphosphole-2-oxides prepared in this invention are defined generally by the formula ##STR1## wherein R is an alkyl containing from one to five carbon atoms and X and Y each represent substituents such as unsubstituted or halogen-substituted alkyl, alkenyl or alkoxy, cyano, alkylsulfonyl, alkoxycarbonyl or halo groups which do not interfere with the reaction.
Compounds of Formula I can be prepared by treating a 2-nitrodiphenylamine ##STR2## with a trialkyl phosphite, (RO)3 P. The trialkyl phosphite is preferably trimethyl phosphite or triethyl phosphite. The 2-nitrodiphenylamine may carry substituents X and Y which may be, for example, unsubstituted or substituted alkyl or alkoxy, as well as other groups not interfering with the reaction. Depending on the nature of the X and Y substituents, trimethyl phosphite may be preferred in one reaction while triethyl phosphite may be preferred in another reaction. The determination of which trialkyl phosphite should be utilized in a given reaction to make the reaction proceed most efficiently can be determined readily by one skilled in the art with a minimal amount of experimentation. Depending on whether trimethyl phosphite or triethyl phosphite is utilized in the reaction, the reaction products formed in addition to the 2,3-dihydro-1,3,2-benzodiazaphosphole-2-oxide are substantially different. In addition, the time required for the reaction to occur as well as the yield of the desired 1-alkyl-2-alkoxy-3-aryl-2,3-dihydro-1,3,2-benzodiazaphosphole-2-oxide product are different for reactions utilizing trimethyl phosphite and reactions utilizing triethyl phosphite. The structure of the products formed in the instant invention was determined by conventional analytical techniques, infrared spectroscopy, mass spectroscopy, and NMR spectroscopy.
The reaction of 2-nitrodiphenylamine with trimethyl phosphite proceeds according to the equation: ##STR3## The reaction is carried out at elevated temperature, preferably about 80° C. to about 160° C. The length of time required to complete the reaction is dependent upon the temperature. When the solution of 2-nitrodiphenylamine and trimethyl phosphite is heated to reflux, the reaction proceeds with trimethyl phosphate and dimethyl methyl phosphonate being the only reaction products formed in addition to 1-alkyl-2-alkoxy-3-aryl-2,3-dihydro-1,3,2-benzodiazaphosphole-2-oxide. After a sufficient amount of time has passed for all of the 2-nitrodiphenylamine to react, continued heating at temperatures ranging from about 190° C. to about 210° C. causes rupture of both P--N bonds in Formula I. This eventually results in the conversion of all of the 1-alkyl-2-alkoxy-3-aryl-2,3-dihydro-1,3,2-benzodiazaphosphole-2-oxide to 2-dimethylamino-N-methyldiphenylamine.
By contrast, the reaction of 2-nitrodiphenylamine with triethyl phosphite leads to the formation of a phosporamidate and 2,3-dihydro-1,3,2-benzodiazaphosphole-2-oxide derivative. The reaction proceeds according to the equation: ##STR4## The reaction is carried out at a temperature ranging from about 130° C. to about 165° C. The length of time required for the desired reaction to occur is dependent on temperature and is not critical. When the reaction temperature is maintained at reflux over prolonged periods of time (3-5 days), which is about 180° C. to about 220° C., the products formed are 2-(diethylamino)diphenylamine, 2-(diethylamino)-N-ethyldiphenylamine, and a mixture of tetraethylated ortho-aminodiphenylamines.
Compounds prepared by the process of the invention are suitable for use as intermediates for pharmaceuticals as well as organic ligands such as, for example, a phosphine ligand in a carbonylation reaction.
The invention is further described the by following examples which are intended for illustration and are not to be construed as limiting the invention.
EXAMPLE 1
Preparation of 2,3-dihydro-2-methoxy-3-methyl-1-phenyl-1,3,2-benzodiazaphosphole-2-oxide.
A solution of 10.7 g (0.05 mole) of 2-nitrodiphenylamine in 150 ml of trimethyl phosphite was heated at reflux for 28 hours. The solution was then cooled, poured into 200 ml of aqueous 10% hydrochloric acid and extracted with 3×200 ml of ether. The ethereal extracts were dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by silica chromatography to give a syrup, that was crystallized from 1:1 v:v ether:hexane to give 2,3-dihydro-2-methoxy-3-methyl-1-phenyl-1,3,2-benzodiazaphosphole-2-oxide.
EXAMPLE 2
Preparation of 2,3-dihydro-2-ethoxy-3-ethyl-1-phenyl-1,3,2-benzodiazaphosphole-2-oxide.
A solution of 10.7 g (0.05 mole) of 2-nitrodiphenylamine in 50 ml of triethyl phosphite was heated to reflux (160±5° C.). The course of the reaction was monitored by thin layer chromatography. After 5 hours, the reaction was concentrated under rotary evaporation (0.5 mm, 90° C.). The residual oil was then purified by silica chromatography to give a first fraction consisting of red syrup that crystallized from ether to give solid diethyl N-(2-(phenylaminophenyl)phosphoramidate. The second fraction consisted of 2,3-dihydro-2-ethoxy-3-ethyl-1-phenyl-1,3,2-benzodiazaphosphole-2-oxide, an amber red oil.
EXAMPLE 3
Preparation of propionic acid, 2-(4-(2-ethoxy-3-ethyl-2,3-dihydro-2-oxo-5-(trifluoromethyl)-1,3,2-benzodiazaphosphol-1-yl)phenoxy)-, ethyl ester.
A solution of 10.0 g (0.025 mole) of propanoic acid, 2-(4-(2-nitro-4-(trifluoromethyl)phenyl)amino)phenoxy)-, ethyl ester in 50 ml of triethyl phosphite was heated at 150° C. (reflux) for 3 hours until thin layer chromatography showed disappearance of starting material. The mixture was then concentrated under reduced pressure (1 mm, 80° C.). The residue was purified by silica chromatography to yield propionic acid, 2-(4-(2-ethoxy-3-ethyl-2,3-dihydro-2-oxo-5-(trifluoromethyl)-1,3,2-benzodiazaphosphol-1-yl)phenoxy)-, ethyl ester.

Claims (3)

We claim as our invention:
1. A process for preparing a compound of the formula ##STR5## which comprises treating 2-nitro-diphenylamine of the formula ##STR6## with a trialkyl phosphite (RO)3 P, R being an alkyl of up to five carbon atoms, X and Y each representing an unsubstituted or halogen-substituted alkyl, alkenyl or alkoxy, cyano, alkylsulfonyl, alkoxycarbonyl or a halo group at a temperature ranging from about 80° C. to about 165° C.
2. The process of claim 1 wherein the trialkyl phosphite is trimethyl phosphite.
3. The process of claim 1 wherein the trialkyl phosphite is triethyl phosphite.
US06/811,067 1985-12-19 1985-12-19 Preparation of 2,3-dihydro-1,3,2-benzodiazaphosphole-2-oxides Expired - Lifetime US4659858A (en)

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Citations (1)

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Publication number Priority date Publication date Assignee Title
US3116309A (en) * 1961-09-28 1963-12-31 Shell Oil Co Heterocyclic compounds containing ring carbon, nitrogen and phosphorus or arsenic atoms and their preparation

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3116309A (en) * 1961-09-28 1963-12-31 Shell Oil Co Heterocyclic compounds containing ring carbon, nitrogen and phosphorus or arsenic atoms and their preparation

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